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PubMed2005

Exploring nonlinear association between prenatal methylmercury exposure from fish consumption and child development: evaluation of the Seychelles Child Development Study nine-year data using semiparametric additive models.

Studies of the association between prenatal methylmercury exposure from maternal fish consumption and neurodevelopmental test scores in the Seychelles Child Development Study have not found adverse effects through age 9 years. The analysis for the most recent 9-year data (Lancet 361 (2003) 1686) employed conventional linear regression models. In this study we reanalyzed the same Seychelles 9-year data using semiparametric additive models with different degrees of smoothing to explore whether nonlinear effects of prenatal exposure were present. Of 21 endpoints in the linear analysis, we chose only those with a two-tailed P value less than 0.2 for the effect of prenatal exposure. Six endpoints met the criterion. A nonlinear effect was identified with the more smooth model for only one endpoint. The test for an overall effect of prenatal exposure was also significant, with a P value of 0.04, while the corresponding P value in the linear regression analysis was 0.08. The nonlinear curve appeared to be nearly flat when the level was below approximately 12 ppm in maternal hair, with a linear trend above that level, suggesting a possible adverse effect in the uppermost range of prenatal exposure included in this cohort. Because of the descriptive nature of semiparametric additive models, the P values are not precise, and certainly there are fewer data above 12 ppm. We conclude that this reanalysis supports the primary linear analysis, showing little evidence for a prenatal adverse effect.

Child↗

PubMed2003

Effects of polyvinyl alcohol administered in the diet to rats on fertility, early embryonic development, growth and development.

PVA was administered in the diet to male and female Sprague-Dawley rats (26/sex/group) at doses of 0, 2000, 3500 and 5000 mg/kg/day for two generations. The study design assessed gonadal function, estrous cycle, mating behavior, conception, gestation, parturition, lactation, weaning, and growth and development of F(1) and F(2) offspring. Parental rats were treated for 70 days prior to mating, throughout mating, gestation and lactation until sacrifice. Clinical observations, body weights and feed consumption were recorded routinely. Dietary concentrations were adjusted for each sex on a weekly basis except during gestation and lactation, to provide the intended mg/kg/day PVA levels. Pups were weighed routinely and weaned at 21 days of age prior to selection for the next generation. Unformed stool was noted predominately at the 3500 and 5000 mg/kg/day levels in P(0) and F(1) parental animals. This finding was attributed to the high levels of PVA being fed and subsequently excreted in the stool. Slight decreases in the mean body weights of P(0) males were noted at 2000 and 5000 mg/kg/day. Feed consumption was elevated at the 3500 and 5000 mg/kg/day doses in both generations but not during either lactation period. These increases generally were observed in a dose-related manner (g/kg/day), as a result of the large amount of PVA being consumed to maintain the caloric intake necessary for normal growth. There were no effects of PVA on P(0), F(1) male or female reproductive performance or pup survival, growth, organ weights, and macroscopic or microscopic observations at doses of 2000, 3500 and 5000 mg/kg/day. Therefore the no-observed-effect level (NOAEL) is 5000 mg/kg/day for both parental and offspring in this reproductive study.

Administration, Oral↗

PubMed1998

How to develop a group curriculum: developing an exercise programme for overweight adults.

This paper reports on work to develop introductory exercise courses for sedentary, moderately overweight adults. The aim is to offer a safe and motivating programme of physical exercise and, through experiential learning, to encourage and facilitate increased physical activity. The core of the programme is a course of 10-20 weekly exercise classes. The classes include a variety of physical exercises adapted to the special needs of overweight adults (BMI 28-34 kg/m2) and a number of health-related fitness tests. We outline the underlying principles of the exercise courses, their structure and contents, the guidelines of instruction, and the use of formative evaluation. In addition, we report on the implementation of five weight-reduction courses and six exercise courses involving a total of 209 participants. A fairly high level of programme acceptability (in terms of attendance rates and personal commitment) and programme feasibility (in terms of acceptability, changes in personal orientation towards health and weight reduction, and satisfaction among participants) was achieved.

Adolescent↗

PubMed2000

Preventing mother-to-child transmission of HIV in developing countries: recent developments and ethical implications.

Various regimens of antiretroviral (ARV) therapy during pregnancy and labour have been found to be effective in reducing the risk of mother-to-child transmission of HIV. Cost and late identification of women with HIV infection during pregnancy in many developing countries have been the impetus to study inexpensive, short-course ARV regimens. Recently, it was shown that a single dose of nevirapine given orally once during labour to the mother and once to the infant greatly reduces the risk of HIV transmission. As a result, it has been proposed that in high HIV prevalence areas, this drug regimen be offered routinely to all pregnant women and their infants, without the need for an HIV test. This is seen as a cost-effective alternative to trying to make voluntary HIV testing and counselling universally available to pregnant women, which would require improved antenatal uptake and care, high uptake of HIV testing and high rates of return to learn results before women could make decisions regarding ARV prophylaxis. The ethical dilemmas arising from both these options are currently under debate, against a backdrop of concerns about breastfeeding and breastmilk substitutes, what to do about the increasing numbers of AIDS orphans and how to prevent HIV transmission to women in the first place.

Anti-HIV Agents↗

PubMed1998

Social context in developmental psychopathology: recommendations for future research from the MacArthur Network on Psychopathology and Development. The MacArthur Foundation Research Network on Psychopathology and Development.

Accumulating evidence suggests that social contexts in early life have important and complex effects on childhood psychopathology. Spurred by the lack of an explicit operational definition that could guide the study of such effects, we define a social context operationally as "a set of interpersonal conditions, relevant to a particular behavior or disorder and external to, but shaped and interpreted by, the individual child." Building on this definition, we offer a series of recommendations for future research, based on five theoretically derived propositions: (a) Contexts are nested and multidimensional; (b) contexts broaden, differentiate, and deepen with age, becoming more specific in their effects; (c) contexts and children are mutually determining; (d) a context's meaning to the child determines its effects on the child and arises from the context's ability to provide for fundamental needs; and (e) contexts should be selected for assessment in light of specific questions or outcomes. As reflected in an increasingly rich legacy of literature on child development and psychopathology, social contexts appear to influence emerging mental disorders through dynamic, bidirectional interactions with individual children. Future research will benefit from examining not only statistical interactions between child- and context-specific factors, but also the actual transactions between children and contexts and the transduction of contextual influences into pathways of biological mediation. Because adverse contexts exert powerful effects on the mental health of children, it is important for the field to generate new, more theoretically grounded research addressing the contextual determinants of psychological well-being and disorder.

Child↗

PubMed1975

Plastid development in primary leaves of Phaseolus vulgaris. Development of plastid adenosine triphosphatase activity during greening.

The etioplasts of dark-grown bean leaves showed ATPase (adenosine triphosphatase) activity which had a pH optimum of 8.5, was stimulated by dithiothreitol and unaffected by light-triggering. Bean chloroplasts showed a low activity of dark-induced ATPase with a pH optimum of 8.5 and a substantial amount of light-triggered activity with a pH optimum of 8.0. The light-triggered activity depended on dithiothreitol and Mg2+ and was promoted by phenazine methosulphate. Light-triggered ATPase activity was completely inhibited by 20mum-dicyclohexylcarbodi-imide. Etioplasts developed light-triggered ATPase activity in response to 30 min illumination of the etiolated leaves. During the 48 h of light-induced greening of dark-grown leaves there was a 70% increase of the chloroplast ATPase activity found after light-triggering and a 30% fall in the dark-induced activity, both expressed on a per leaf basis. As the larger part of these changes occurred during the first 30 min of illumination, it is concluded that most or all of the chloroplast ATPase was present in the etioplast, a conclusion identical with that of Lockshin et al. (1971) for maize. During 48 h of greening there was a tenfold increase in the amount of thylakoid membrane in the leaf together with an 83% fall in the ATPase activity per m2 of thylakoid membrane, measured after light-triggering.

Adenosine Triphosphatases↗

PubMed1998

Towards new partnerships for health development in developing countries: the contractual approach as a policy tool.

What roles for government but also for society's groups in the advancement of public health in developing countries? This paper focuses on the need to adopt the contractual approach as a powerful policy tool and sketches the contours of a policy framework for good contracting. A short historical review of health system changes leads up to a discussion of the current emergence of a multitude of actors, the forging of alliances between the various partners, examples on how significant health policy benefits might be secured through contracting, and the implications of building alliances, such as defining and assigning accountability to the contracting partners.

Developing Countries↗

PubMed2002

Developing a positive organisational culture using a management development strategy.

This paper evaluates a management development program, which was piloted at Albury Base Hospital during 2001 for nurse managers. The program uses quantitative assessments of participants using a lifestyle inventory tool and enables managers to identify opportunities and strategies to assist them to become more effective managers. The program also helps identify management "blind spots" and increased awareness of the effect of management's behaviour on team efficiency. The program was evaluated as being relevant to managers from any health discipline and was a means by which workplace culture and behaviour could be improved.

Efficiency, Organizational↗

PubMed2005

Understanding cellular disruptions during early embryo development that perturb viability and fetal development.

An inability to regulate ionic and metabolic homeostasis is related to a reduction in the developmental capacity of the embryo. The early embryo soon after fertilisation and up until compaction appears to have a reduced capacity to regulate its homeostasis. The reduced ability to regulate homeostasis, such as intracellular pH and calcium levels, by the precompaction-stage embryo appears to impact on the ability to regulate mitochondrial function and maintain adequate levels of energy production. This reduction in ATP production causes a cascade of events leading to disrupted cellular function and, perhaps ultimately, disrupted epigenetic regulation and aberrant placental and fetal development. In contrast, after compaction the embryo takes on a more somatic cell-like physiology and is better able to regulate its physiology and therefore appears less vulnerable to stress. Therefore, for human IVF it would seem important for the establishment of healthy pregnancies that the embryos are maintained in systems that are designed to minimise homeostatic stress, particularly for the cleavage-stage embryos, as exposure to stress is likely to culminate in impaired embryo function.

Adenosine Triphosphate↗

PubMed2002

Early attachment security, subsequent maternal sensitivity, and later child development: does continuity in development depend upon continuity of caregiving?

In order to test the hypothesis (1) that the most competent 3-year-olds would be those with histories of secure attachment (at 15 months) who subsequently experienced (relatively) high-sensitive mothering (at 24 months), (2) that the least competent children would be those with histories of insecure attachment who subsequently experienced (relatively) low-sensitive mothering, and (3) that those with mixed or inconsistent attachment-sensitivity histories would fall in between, data gathered as part of the NICHD Study of Early Child Care were examined. A-priori tests supported the hypothesis in the case of all five developmental outcomes examined (problem behavior, social competence, expressive language, receptive language, school readiness), though group means did not always rank in the predicted direction. Further planned comparisons of children with mixed attachment-sensitivity histories revealed that, in the case of all outcomes, insecurely attached children who subsequently experienced high-sensitive mothering significantly outperformed secure children who subsequently experienced low-sensitive mothering. Follow-up analyses highlighted the role of maternal and family stress in accounting for why some infants who were classified as secure at 15 months experienced low-sensitive mothering at 24 months and why some infants classified as insecure subsequently experienced high-sensitive mothering. Results are discussed with regard to the role of early experience in shaping development.

Adaptation, Psychological↗

PubMed1995

Blastocyst development in co-culture: development and morphological aspects.

A retrospective study was undertaken to determine if initial culture conditions and embryo quality had an effect on subsequent blastocyst development in co-culture for cryopreservation. The apparent effects of freeze-thawing on blastocysts at the ultrastructure level were also observed. On day 3 of culture, embryos were categorized into two groups based on their morphological attributes. Results suggest that the initial culture environment of embryos up to day 3 (5- to 8-cell stage) did not affect the subsequent rate of blastocyst formation in co-culture. However, the initial embryo quality had an impact on blastocyst formation and quality. On day 5.5, 90% (60/67) of the optimal quality embryos (six to eight blastomeres with minimal or no fragmentation on day 3) had attained the blastocyst stage, which was greater (P < 0.01) than the 55% (31/56) observed with the sub-optimal embryos (five to eight blastomeres with 30-50% fragmentation on day 3). Furthermore, 66% (44/67) of embryos initially graded as optimal were suitable for cryopreservation, which was greater (P < 0.01) than attained with embryos of lesser quality (22/56; 39%). At the ultrastructural level, the polarized distribution of plasma membrane microvilli was retained, as was the integrity of the nuclear membrane following thawing.

Blastocyst↗

PubMed1995

The Twelfth Jack Tizard Memorial Lecture. The development of offending and antisocial behaviour from childhood: key findings from the Cambridge Study in Delinquent Development.

In the Cambridge Study in Delinquent Development, 411 South London males have been followed up from age 8 to age 32. The most important childhood (age 8-10) predictors of delinquency were antisocial child behaviour, impulsivity, low intelligence and attainment, family criminality, poverty and poor parental child-rearing behaviour. Offending was only one element of a larger syndrome of antisocial behaviour that arose in childhood and persisted into adulthood. Marriage, employment and moving out of London fostered desistance from offending. Early prevention experiments are needed to reduce delinquency, targeting low attainment, poor parenting, impulsivity and poverty.

Adolescent↗

PubMed2004

Outcomes of a national faculty development program in teaching skills: prospective follow-up of 110 medicine faculty development teams.

BACKGROUND: Awareness of the need for ambulatory care teaching skills training for clinician-educators is increasing. A recent Health Resources and Services Administration (HRSA)-funded national initiative trained 110 teams from U.S. teaching hospitals to implement local faculty development (FD) in teaching skills. OBJECTIVE: To assess the rate of successful implementation of local FD initiatives by these teams. METHODS: A prospective observational study followed the 110 teams for up to 24 months. Self-reported implementation, our outcome, was defined as the time from the training conference until the team reported that implementation of their FD project was completely accomplished. Factors associated with success were assessed using Kaplan-Meier analysis. RESULTS: The median follow-up was 18 months. Fifty-nine of the teams (54%) implemented their local FD project and subsequently trained over 1,400 faculty, of whom over 500 were community based. Teams that implemented their FD projects were more likely than those that did not to have the following attributes: met more frequently (P=.001), had less turnover (P=.01), had protected time (P=.01), rated their likelihood of success high (P=.03), had some project or institutional funding for FD (P=.03), and came from institutions with more than 75 department of medicine faculty (P=.03). The cost to the HRSA was $22,033 per successful team and $533 per faculty member trained. CONCLUSIONS: This national initiative was able to disseminate teaching skills training to large numbers of faculty at modest cost. Smaller teaching hospitals may have limited success without additional support or targeted funding.

Education, Medical, Continuing↗

PubMed2003

Faculty development: how to evaluate the effectiveness of a faculty development program in emergency medicine.

Evaluation of the effectiveness of any faculty development program (FDP) is crucial to provide assessment of existing programs and to yield valid recommendations for designing future programs that better address the needs of individual faculty members and the sponsoring institutions. The author chose the validated Kirkpatrick's model with four levels of program outcomes (satisfaction data, learning data, performing data, and career change) to evaluate the effectiveness of an FDP in emergency medicine. Assessment of the effectiveness of this FDP can be performed by sponsoring organizations or by independent evaluators experienced in the field for better objectivity.

Emergency Medicine↗

PubMed2003

Functional and morphological development of lymphoid tissues and immune regulatory and effector function in rhesus monkeys: cytokine-secreting cells, immunoglobulin-secreting cells, and CD5(+) B-1 cells appear early in fetal development.

Little is known regarding the timing of immune ontogeny and effector function in fetal humans and nonhuman primates. We studied the organization of lymphocyte and antigen-presenting cell populations in developing lymphoid tissues of rhesus monkey fetuses during the second and third trimesters (65 to 145 days of gestation; term = 165 days). Immunoglobulin-secreting and cytokine-secreting cells were detected at day 80. The thymus, spleen, lymph nodes, and intestinal mucosa were examined for cells expressing CD3, CD5, CD20, CD68, p55, and HLA-DR. In the spleens of 65-day-old fetuses (early second trimester), the overwhelming majority of total lymphocytes were CD5(+) CD20(+) B-1 cells. The remaining lymphocytes were CD3(+) T cells. By day 80, splenic B and T cells were equal in number. Intraepithelial CD3(+) CD5(-) T cells and lamina propria CD20(+) CD5(+) B cells were present in the intestines of 65-day-old fetuses. By day 80, numerous CD20(+) CD5(+) B cells were present in the jejunums and colons and early lymphocyte aggregate formation was evident. The spleens of 80- to 145-day-old fetuses contained immunoglobulin M (IgM)-secreting cells, while IgA-, IgG-, interleukin-6-, and gamma interferon-secreting cells were numerous in the spleens and colons. Thus, by the second trimester, the lymphoid tissues of the rhesus monkey fetus have a complete repertoire of properly organized antigen-presenting cells, T cells, and B cells.

Animals↗

PubMed1976

The development of creatine kinase in rat skeletal muscle. Changes in isoenzyme ratio, protein, RNA and DNA during development.

The activity of cytosolic creatine kinase in rat skeletal muscle rises stepwise during development. The increases occur simultnaeously with transient increases in DNA content. The second increase is accompanied by a rise in total protein, soluble sarcoplasmic protein and RNA/DNA ratio. Such changes are not observed at 20 days after birth, when creatine kinase finally accumulates to the adult level. Transient higher amounts of the MB and BB isoenzymes are observed after the first and second stepwise increase. The increase in creatine kinase activity observed after birth is predominantly due to an activation of the M gene. The BB isoenzyme is still present in adult skeletal muscle, but contributes little to the total activity.

Age Factors↗

PubMed2002

Research and development of transgenic plants in Malaysia: an example from an Asian developing country.

In 2000, agriculture contributed 13% to the national gross domestic product of Malaysia. The country of 23 million people has created a competitive program coordinated by the Ministry of Science, Technology and the Environment, research institutions, and universities to undertake biotechnology research in several areas. Intensified research efforts are under way on oil palm, rubber, rice, papaya, and orchids. Although the most progress has been made in rice and papaya, no transgenic crop is ready for field trials. Nonetheless, preliminary steps have been taken to prepare for the trials, and detailed testing protocols are being developed.

Agriculture↗

PubMed2005

Plastids unleashed: their development and their integration in plant development.

Derived by endosymbiosis from ancestral cyanobacteria, chloroplasts integrated seamlessly into the biology of their host cell. That integration involved a massive transfer of genes to the cell's nucleus, with the modification of pre-existing processes, like plastid division and the operation of the plastid genetic machinery and the emergence of new ones, like the import of proteins translated in the cytoplasm. The uncovering in molecular detail of several of these processes reveals a merger of mechanisms of symbiont and host origin. Chloroplasts acquired roles as part of the biology of land plants by differentiating into a variety of interconvertible plastid forms according to the cell type. How these conversions take place, or how new problems, like the regulation of the plastid population size in cells, have been solved, is barely starting to be understood. Like the whole plant and as a result of the requirements and dangers associated with photosynthetic activity, chloroplasts in particular are under the control of environmental cues. Far from being passive targets of cellular processes, plastids are sources of signals of plastid-nuclear communication, which regulate activities for their own biogenesis. Plastids are also sources of developmental signals, in whose absence tissue architecture or cell differentiation are aberrant, in a cell-autonomous fashion. Over evolutionary time, plastids also contributed many genes for activities that are no longer directly associated with them (like light perception or hormone function). The overall picture is one in which plastids are at both the receiving and the acting ends in plant development, in both ontogenic and evolutionary terms.

Biological Evolution↗